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PCB52 exposure alters the neurotransmission ligand-receptors in male offspring and contributes to sex-specific neurodevelopmental toxicity
2020
Zhao, Dong | Wang, Qi | Zhou, Wen-Tao | Wang, Li-Bin | Yu, Hao | Zhang, Kai-Kai | Chen, Li-Jian | Xie, Xiao-Li
Polychlorinated biphenyls (PCBs) in the air are predominantly the less chlorinated congeners. Non-dioxin-like (NDL) low-chlorinated PCBs are more neurotoxic, and cause neurodevelopmental and neurobehavioral alterations in humans. However, the underlying mechanisms for this neurodevelopmental toxicity remain unknown. In the present study, Wistar rats were treated by gavage with PCB52 (1 mg/kg body weight) or corn oil from gestational day 7 to postnatal day 21. Both the body lengths and weights of the suckling rats at birth were significantly decreased by PCB52 treatment, suggesting developmental toxicity. Although no obvious histopathological changes were observed in the brain, using RNA-sequencing, 208 differentially expressed genes (DEGs) were identified in the striatum of PCB52-treated male offspring, while just 13 DEGs were identified in female offspring, suggesting sex-specific effects. Furthermore, using Gene Ontology enrichment analysis, neurodevelopmental processes, neurobehavioral alterations, and neurotransmission changes were enriched from the 208 DEGs in male offspring. Similarly, using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, neuroactive ligand receptor interactions and multiple synapse pathways were enriched in male offspring, implying dysfunction of the neurotransmission system. Reductions in the protein expressions of these ligand receptors were also identified in the striatum, cerebral cortex, and hippocampus using western blotting methods. Taken together, our findings indicate that PCB52 exposure during gestation and lactation results in the abnormal expression of neurotransmission ligand-receptors in male offspring with a sex bias, and that this may contribute to neurodevelopmental toxicity.
اظهر المزيد [+] اقل [-]Parabens in breast milk and possible sources of exposure among lactating women in Korea
2019
Park, Na-Youn | Cho, Yoon Hee | Choi, Kyungho | Lee, Eun-hee | Kim, Yang Jee | Kim, Jung Hoan | Kho, Younglim
Parabens, broad-spectrum antimicrobial preservatives widely used in various consumer products and food, are suspected to be linked with several adverse health effects in humans, especially newborn babies, infants, and young children. While human exposure to parabens has been frequently reported by measuring the concentration of parabens in urine, similar measurements in breast milk have rarely been made. To determine paraben concentrations in breast milk and possible sources of exposure, four major parabens, including methylparaben (MP), ethylparaben (EP), propylparaben (PP), and butylparaben (BP) were measured in breast milk samples collected from 260 lactating women in South Korea. Demographic, socioeconomic, and behavioral factors associated with the presence of parabens in breast milk were determined. EP concentrations were detected at the highest levels in breast milk samples, followed by MP, PP, and BP. Pre-pregnancy BMI, parity, use of basic skin care products, use of cosmetics, canned beverage, and type of milk consumption were associated with higher frequencies of paraben detection. In addition, type of milk, parity, and drinking status were significantly associated with the concentration of EP. Multiple regression analyses showed that colostrum and transitional milk samples had higher levels of EP than mature milk samples. The estimated daily intake of parabens in infants via breastfeeding appears to be negligible when compared to the acceptable daily intake values set forth by the European Food Safety Authority (EFSA); however, considering the vulnerability of breastfed infants and ubiquitous sources of exposure from daily use of household and personal toiletries, efforts to identify sources and mitigate exposure are warranted.
اظهر المزيد [+] اقل [-]Maternal transfer of phenol derivatives in the Baltic grey seal Halichoerus grypus grypus
2018
Nehring, Iga | Falkowska, Lucyna | Staniszewska, Marta | Pawliczka, Iwona | Bodziach, Karina
Studies of circulating levels in difference sex and age classes, and maternal transfer of bisphenol A, 4-tert-octylphenol and 4- nonylphenol in the Baltic grey seal were performed from 2014-2017. Blood was collected from long-term captive adult males, pregnant females and pups. Milk was collected from nursing females. The aim of this study was not only to determine the concentrations of phenol derivatives, i.e. bisphenol A (BPA), 4-tert-octylphenol (OP) and 4-nonylphenol (NP), but also to try to evaluate the transfer of these compounds to the next generation in the final stage of foetal life and in the first few weeks of life in juvenile marine mammals. The measurements were carried out using high performance liquid chromatography. The obtained data show that all phenol derivatives are present in the blood of males, females and pups (range <0.07–101 ng·cm⁻³) and in female milk (range <0.1–406.3 ng·cm⁻³). The main source of phenol derivatives in organisms is food exposure. Gender, age, or number of births were not observed to have a significant effect on changes in phenol derivative levels in seal blood within the breeding group. In the prenatal stage of life, a small amount of BPA and alkylphenols was passed on to the offspring through the placenta. In the blood of the offspring the concentration of these compounds exceeded the concentration in the mother's blood 1.5-fold. During nursing, females detoxified their systems. Level of phenol derivatives in the pups blood increased linearly with its increasing concentrations in the mother's milk. On the other hand, the seafood diet which started after the physiological fasting stage of the pup, stabilised the levels of phenol derivatives below 10 ng ∙ cm⁻³.
اظهر المزيد [+] اقل [-]Blood dynamics of mercury and selenium in northern elephant seals during the lactation period
2011
The effects of reproduction and maternal investment (i.e., milk transfer) on trace element levels remain poorly understood in marine mammals. We examined the blood dynamics of mercury (Hg) and selenium (Se) during lactation in the northern elephant seal (Mirounga angustirostris), a top predator from the North Pacific Ocean. Total Hg and Se levels were measured in whole blood and milk of 10 mother–pup pairs on days 5 and 22 of lactation. Both Hg and Se were transferred to offspring through the milk. Results suggested that the maternal transfer of Se was prominent during lactation, whereas the Hg transfer was larger during gestation. The lactation period affected Hg and Se levels in the blood of elephant seal mothers and pups. Physiological processes and their relationship to body condition should be considered carefully when interpreting trace element levels in the framework of biomonitoring.
اظهر المزيد [+] اقل [-]National survey of the levels of persistent organochlorine pesticides in the breast milk of mothers in China
2011
Zhou, Pingping | Wu, Yongning | Yin, Shian | Li, Jingguang | Zhao, Yunfeng | Zhang, Lei | Chen, Huijing | Liu, Yinping | Yang, Xin | Li, Xiaowei
The occurrence of persistent organochlorine pesticides (OCPs) in breast milk samples collected from mothers from twelve provinces in mainland China was investigated. Dichlorodiphenyltrichloroethanes (DDTs) were the most prevalent agent, followed by HCHs and HCB, whereas levels of chlordane compounds, drins and mirex were lower. The relatively lower DDE/DDT ratio in the Fujian rural area suggested more recent exposure to DDT than in other areas. The mean level of DDTs in breast milk from the southern China was higher than those from northern China (p < 0.05). A positive correlation was observed between concentration of DDTs in human milk and consumption of animal-origin food, suggesting that this parameter could play an important part in influencing OCPs burdens in lactating women. The mean estimated daily intakes of different OCPs for breastfed infants were lower than the tolerable daily intake.
اظهر المزيد [+] اقل [-]Impaired sperm quantity and motility in adult rats following gestational and lactational exposure to environmentally relevant levels of PBDE-47: A potential role of thyroid hormones disruption
2021
Li, Xiaoning | Gao, Hui | Li, Pei | Chen, Wei | Tang, Sha | Liu, Luming | Zhou, Guoyu | Xia, Tao | Wang, Aiguo | Zhang, Shun
Polybrominated diphenyl ethers (PBDEs) are flame retardants and the congener 2, 2′, 4, 4′-tetrabromodiphenyl ether (PBDE-47) is capable of inducing thyroid endocrine disruption and developmental toxicity. However, little is known about whether developmental PBDE-47 exposure-elicited alterations in semen quality is associated with thyroid hormones (THs) perturbation. In this research, we sought to explore the impacts of gestational and lactational PBDE-47 exposure on adult sperm quantity and motility, and its link with THs levels. For this purpose, female Sprague-Dawley rats were administered environmentally relevant PBDE-47 levels (0.1, 1.0, 10 mg/kg/day) by oral gavage from prepregnancy through lactation cessation to achieve early-life exposure of offspring and to mimic the actual exposure. Sperm quantity and motility together with serum THs levels from male offspring were determined on postnatal day 88. In utero and lactational exposure to PBDE-47 boosted the weight gain while reduced the relative testis weight in adult male offspring. These were accompanied with the reductions in sperm counts (total and living sperm counts), the percentage of progressive sperm motility, sperm velocities (curvilinear velocity, straight-line velocity and average path velocity), motion path (beat cross frequency, linearity and wobble) and linear motile sperm parameters (count, motility and concentration). Further studies identified that the levels of serum triiodothyronine (T₃) were increased by PBDE-47 exposure and negatively associated with those differential semen parameters on quantity and motility. Collectively, our results indicate that exposure to low-level PBDE-47 during early-life development impairs semen quality in adult rats, which could be mediated partially by abnormal T₃ levels.
اظهر المزيد [+] اقل [-]Exposure to acrylamide induces skeletal developmental toxicity in zebrafish and rat embryos
2021
Zhu, Fanghuan | Wang, Jun | Jiao, Jingjing | Zhang, Yu
Acrylamide is a well-known carcinogen and neurotoxic substance that has been discovered in frying or baking carbohydrate-rich foods and is widely found in soils and groundwater. The purpose of this study was to investigate the adverse effects of exposure to acrylamide on skeletal development. After treatment with acrylamide in zebrafish embryos, the survival and hatching rates decreased, and the body length shortened, with cartilage malformation and a decrease in skeletal area. Exposure to acrylamide in maternal rats during the lactation period disturbed bone mineral density, serum levels of parathyroid hormone, and the expression of skeletal development-related genes in neonates. Exposure to acrylamide in pregnant rats during the pregnancy period decreased the trabecular density and inhibited cartilage formation by delaying the differentiation of osteoblasts and promoting the maturation of osteoclasts in rat embryos. Furthermore, acrylamide intervention downregulated the expression of chondrocyte and osteoblast differentiation-related genes (sox9a, bmp2, col2a1, and runx2), and upregulated the expression of osteoclast marker genes (rankl and mcsf) in zebrafish and rat embryos at different gestational stages. Our results indicated that exposure to acrylamide dysregulated signature gene and protein expression profiles of skeletal development by suppressing the differentiation and maturation of osteoblasts and cartilage matrix and promoting the formation of osteoclasts, and ultimately induced skeletal abnormality in morphology, which brings increasing attention to the intergenerational toxicity of acrylamide via mother-to-child transmission.
اظهر المزيد [+] اقل [-]Bisphenol analogue concentrations in human breast milk and their associations with postnatal infant growth
2020
Jin, Hangbiao | Xie, Jiahui | Mao, Lingling | Zhao, Meirong | Bai, Xiaoxia | Wen, Jie | Shen, Tao | Wu, Pengfei
Many studies show that bisphenol A (BPA) is widespread in human breast milk. However, the occurrence of other bisphenol analogues (BPs), including bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF), in breast milk is still not well known. In this study, breast milk samples were collected from 190 women in Hangzhou, China, with the aims to characterize the occurrence of BPA, BPS, BPF, and BPAF in these samples and to investigate their effects on postnatal growth of infants through breast milk consumption. BPA (mean 2.5 ng/mL, range < LOD–15 ng/mL) was the most abundant BP in breast milk, followed by BPS (0.19 ng/mL, <LOD–1.3 ng/mL) and BPAF (0.092 ng/mL, <LOD–0.58 ng/mL). BPF was not detected in all breast milk samples. We firstly found that breast milk concentrations of BPA were negatively correlated with infant’s weight or length gain rate. Daily intakes (DIs) of BPs via the consumption of breast milk were calculated for infants, and the mean DI values were 531 ng/kg/day, 53 ng/kg/day, and 24 ng/kg/day for BPA, BPS, and BPAF, respectively. Overall, this study firstly demonstrats that the lactation exposure to BPA through breast milk consumption may affect the postnatal growth of infants.
اظهر المزيد [+] اقل [-]Regulation of lipid droplets via the PLCβ2-PKCα-ADRP pathway in granulosa cells exposed to cadmium
2020
In steroidogenic cells, steroids are synthesized de novo from cholesterol stored in lipid droplets (LDs). The size of LDs regulated by adipose differentiation-related protein (ADRP) is closely related to cholesterol ester hydrolysis. Many studies reported that cadmium (Cd) had dual effects on steroidogenesis in granulosa cells (GCs). However, the role of LD and its regulation in abnormal steroidogenesis caused by Cd exposure remain unknown. In current study, female rats were exposed to CdCl₂ during gestation and lactation, and influence of such exposure was investigated in ovarian GCs of female offspring. The size of LDs was found much smaller than normal in GCs; ADRP was down-regulated and hormone-sensitive lipase (HSL) phosphorylation was increased, followed by up-regulation of steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (CYP11A1); the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 (PLCβ2) and protein kinase C alpha type (PKCα) were both decreased accompanying the ADRP down-regulation. This series of events resulted in a high level of progesterone in serum. Similar results were demonstrated in GCs treated with 20 μM CdCl₂ for 24 h in vitro. The protein level of ADRP was decreased after gene silencing of PLCβ2/PKCα, and the knockdown of PLCβ2/PKCα/ADRP led to micro-sized LD formation. We found that Cd exposure down-regulated ADRP by inhibiting the PLCβ2-PKCα signaling pathway, reduced the size of LDs, and promoted HSL phosphorylation. StAR and CYP11A1 were both up-regulated following the hydrolysis of cholesterol ester, which led to a high production of progesterone. LD thereby is a target subcellular organelle for Cd to affect steroid hormone synthesis in ovarian GCs. These findings might help to uncover the mechanism of ovarian dysfunction and precocious puberty caused by Cd pollution.
اظهر المزيد [+] اقل [-]Programming of hepatic lipid metabolism in a rat model of postnatal nicotine exposure – Sex-related differences
2020
Bertasso, Iala Milene | Pietrobon, Carla Bruna | Lopes, Bruna Pereira | Peixoto, Thamara Cherem | Soares, Patrícia Novaes | Oliveira, Elaine | Manhães, Alex Christian | Bonfleur, Maria Lucia | Balbo, Sandra Lucinei | Cabral, Suellen Silva | Gabriel Kluck, George Eduardo | Atella, Georgia Correa | Gaspar de Moura, Egberto | Lisboa, Patrícia Cristina
Maternal nicotine exposure during lactation induces liver damage in adult male rats. However, the mechanism in males is unknown and females have not been tested. Here, we determined the liver lipid composition and lipogenic enzymes in male and female offspring at two ages in a model of postnatal nicotine exposure. Osmotic minipumps were implanted in lactating Wistar rat dams at postnatal day (PND) 2 to release 6 mg/kg/day of nicotine (NIC group) or saline (CON group) for 14 days. Offspring received a standard diet from weaning until euthanasia at PND120 (1 pup/litter/sex) or PND180 (2 pups/litter/sex). At PND120, NIC males showed lower plasma triglycerides (TG), steatosis degree 1, higher hepatic cholesterol (CHOL) ester, free fatty acids, monoacylglycerol content as well as acetyl-coa carboxylase-1 (ACC-1) and fatty acid synthase (FAS) protein expression in the liver compared to CON males. At this age, NIC females had preserved hepatocytes architecture, higher plasma CHOL, higher CHOL ester and lower total CHOL content in the liver compared to CON females. At PND180, NIC males showed steatosis degrees 1 and 2, higher TG, lower free fatty acids and total CHOL content in the liver and an increase in ACC-1 hepatic protein expression. NIC females had higher plasma TG and CHOL levels, no change in hepatic morphology, lower CHOL ester and free fatty acids in the liver, which also showed higher total ACC-1 and FAS protein expression. Maternal nicotine exposure induces long-term liver dysfunction, with an alteration in hepatic cytoarchitecture that was aggravated with age in males. Concerning females, despite unchanged hepatic cytoarchitecture, lipid metabolism was compromised, which deserves further attention.
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